In cases of central nervous system (CNS) metastases in NSCLC (brain or leptomeningeal), plasma ctDNA genotyping is constrained by a blood-tumor barrier, and thus alternative sources of ctDNA, such as cerebrospinal fluid, can yield a higher source of ctDNA for the detection of ALK rearrangements [200,201]. The gene discussed is ALK; the disease is neoplasm.